Deciphering Imidazoline Off-Targets by Fishing in the Class A of GPCR field

: Djikic T, Vucicevic J, Laurila J, Radi M, Veljkovic N, Xhaard H, Nikolic K

: 2020

: Molecular Informatics

: Molecular informatics

: Mol Inform

: 39

: 7

: 12

: 1868-1743

: 1868-1751

DOI: https://doi.org/10.1002/minf.201900165

: https://helda.helsinki.fi/bitstream/10138/326822/1/minf.201900165.pdf

Based on the finding that a central antihypertensive agent with high affinity for I1‐type imidazoline receptors – rilmenidine, shows cytotoxic effects on cultured cancer cell lines, it has been suggested that imidazoline receptors agonists might have a therapeutic potential in the cancer therapy. Nevertheless, potential rilmenidine side effects caused by activation of α‐adrenoceptors, or other associated receptors and enzymes, might hinder its therapeutic benefits. Considering that human α‐adrenoceptors belong to the rhodopsin‐like class A of G‐protein‐coupled receptors (GPCRs) it is reasonable to assume that imidazolines might have the affinity for other receptors from the same class. Therefore, to investigate possible off‐target effects of imidazoline ligands we have prepared a reverse docking protocol on class A GPCRs, using imidazoline ligands and their decoys. To verify our in silico results, three ligands with high scores and three ligands with low scores were tested for antagonistic activity on α2‐ adrenoceptors.